Diamox - Quoted from the Physician's Desk Reference, 1993

Diamox is a potent carbonic anhydrase inhibitor, effective
in the control of fluid secretion (e.g. some types of glaucoma),
in the treatment of certain convulsive disorders (e.g. epilepsy),
and in the promotion of diuresis in instances of abnormal
fluid retention (e.g. cardiac edema).

Diamox is an enzyme inhibitor that acts specifically on ...
the hydration of carbon dioxide and the dehydration of
carbonic acid. In the eye, this inhibitory action decreases
the secretion of aqueous humor and results in a drop in
intraocular pressure, a reaction considered desirable in
cases of glaucoma. ... The diuretic effect of Diamox is due
to its action in the kidney on the reversible reaction
involving hydration of carbon dioxide and dehydration of
carbonic acid. The result is renal loss of HCO3 ion, which
carries out sodium, water, and potassium.

Diamox Sequels sustained-release capsules provide prolonged
action to inhibit aqueous humor secretion for 18 to 24
hours after each dose, whereas tablets act for only 8 to 12
hours. ... Blood concentrations of Diamox peak between 3 to 6
hours after administration of Sequels, compared to 1 to 4
hours with tablets.

Placebo-controlled clinical trials have shown that prophylactic
administration of Diamox at a dose of 250mg every 8 to 12 hours
(or 500mg Sequels once daily) before and during rapid ascent
to altitude results in fewer and/or less severe symptoms (such
as headache, nausea, shortness of breath, dizziness, drowsiness,
and fatigue) of acute mountain sickness (AMS). Pulmonary
function is greater in the Diamox treated group, both in
subjects with AMS and asymptomatic subjects. The Diamox
treated climbers also had less difficulty in sleeping.

...

Diamox therapy is contraindicated in situations in which sodium
and/or potassium blod serum levels are depressed, in cases of
marked kidney and liver disease, in suprarenal gland failure,
and in hyperchloremic acidosis. It is contraindicated in
patients with cirrhosis because of the risk of development
of hepatic encephalopathy.

Caution is advised for patients receiving concomitant
high-dose aspirin and Diamox, as anorexia, tachypnea,
lethargy, coma, and death have been reported.

Increasing the dose does not increase the diuresis, and may
increase the incidence of drowsiness and/or paresthesia.
Increasing the dose often results in a decrease in diuresis.

...

Gradual ascent is desirable to try to avoid acute mountain
sickness. If rapid ascent is undertaken and Diamox is used,
it should be noted that such use does not obviate the need
for prompt descent if severe forms of high altitude sickness
occur, i.e. pulmonary edema or cerebral edema.

...

Long term studies in animals to evaluate the carcinogenic
potential of Diamox have not been conducted. In a bacterial
mutagenicity assay, Diamox was not mutagenic when evaluated
with and without metabolic activation.

The drug had no effect on fertility when administered in the
diet to male and female rats at a daily intake of up to four
times the maximum recommended human dose. Diamox has been shown
to produce birth defects of the limbs in mice, rats, hamsters,
and rabbits. There are no adequate and well-controlled studies
in pregnant women. Diamox should be used in pregnancy only if the
potential benefit justifies the potential risk to the fetus.
Because of the potential for serious adverse reactions in nursing
infants from Diamox, a decision should be made whether to discontinue
nursing or to discontinue the drug, taking into account the
importance of the drug to the mother.

The safety and effectiveness of Diamox in children have
not been established.

Adverse reactions, occurring most often early in therapy,
include a "tingling" feeling in the extremities, hearing
dysfunction or tinnitus, loss of appetite, taste alteration
and gastrointestinal disturbances such as nausea, vomiting,
diarrhea, and occasional instances of drowsiness and confusion.

...

No data are available regarding Diamox overdosage in humans as
no cases of acute poisoning with this drug have been reported.
Animal data suggest that Diamox is remarkably non-toxic. No
specific antidote is known. Treatment should be symptomatic
and supportive. Electrolyte imbalance, development of an
acidotic state, and central nervous system effects might be
expected to occur.

...

Dosage is 500mg to 1000mg daily, in divided doses using tablets
or Sequels as appropriate. In circumstances of rapid ascent,
such as in rescue or military operations, the higher dose level
of 1000mg is recommended. It is preferable to initiate dosing
24 to 48 hours before ascent and to continue for 48 hours while
at high altitude, or longer as necessary to control symptoms.